Abstract
Aim:
β-adrenergic receptor (β-AR) agonists are among the most potent factors regulating cardiac electrophysiological properties. Connexin 43 (Cx43), the predominant gap-junction protein in the heart, has an indispensable role in modulating cardiac electric activities by affecting gap-junction function. The present study investigates the effects of short-term stimulation of β-AR subtypes on Cx43 expression and gap junction intercellular communication (GJIC) function.
Methods:
The level of Cx43 expression in neonatal rat cardiomyocytes (NRCM) was detected by a Western blotting assay. The GJIC function was evaluated by scrape loading/dye transfer assay.
Results:
Stimulation of β-AR by the agonist isoproterenol for 5 min induces the up-regulation of nonphosphorylated Cx43 protein level, but not total Cx43. Selective β2-AR inhibitor ICI 118551, but not β1-AR inhibitor CGP20712, could fully abolish the effect. Moreover, pretreatment with both protein kinase A inhibitor H89 and Gi protein inhibitor pertussis toxin also inhibited the isoproterenol-induced increase of nonphosphorylated Cx43 expression. Isoproterenol-induced up-regulation of nonphosphorylated Cx43 is accompanied with enhanced GJIC function.
Conclusion:
Taken together, β2-AR stimulation increases the expression of nonphosphorylated Cx43, thereby enhancing the gating function of gap junctions in cardiac myocytes in both a protein kinase A- and Gi-dependent manner.
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Acknowledgements
This work was supported by the National Key Basic Research Program (NKBRP) of People's Republic of China (No 2006CB503806, 2007CB512008), the National Natural Science Foundation of China (No 30471916, 30821001) and Beijing Municipal Natural Science Foundation (No 7052045).
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Xia, Y., Gong, Kz., Xu, M. et al. Regulation of gap-junction protein connexin 43 by β-adrenergic receptor stimulation in rat cardiomyocytes. Acta Pharmacol Sin 30, 928–934 (2009). https://doi.org/10.1038/aps.2009.92
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DOI: https://doi.org/10.1038/aps.2009.92
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